Structural basis for unfolding pathway-dependent stability of proteins: vectorial unfolding versus global unfolding.


Abstract

Point mutations in proteins can have different effects on protein stability depending on the mechanism of unfolding. In the most interesting case of I27, the Ig-like module of the muscle protein titin, one point mutation (Y9P) yields opposite effects on protein stability during denaturant-induced "global unfolding" versus "vectorial unfolding" by mechanical pulling force or cellular unfolding systems. Here, we assessed the reason for the different effects of the Y9P mutation of I27 on the overall molecular stability and N-terminal unraveling by NMR. We found that the Y9P mutation causes a conformational change that is transmitted through beta-sheet structures to reach the central hydrophobic core in the interior and alters its accessibility to bulk solvent, which leads to destabilization of the hydrophobic core. On the other hand, the Y9P mutation causes a bend in the backbone structure, which leads to the formation of a more stable N-terminal structure probably through enhanced hydrophobic interactions. Study holds ProTherm entries: 25696, 25697, 25698, 25699, 25700 Extra Details: NMR; protein unfolding; titin; mitochondrial protein import; AFM

Submission Details

ID: kRXAbMm8

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:56 p.m.

Version: 1

Publication Details
Yagawa K;Yamano K;Oguro T;Maeda M;Sato T;Momose T;Kawano S;Endo T,Protein Sci. (2010) Structural basis for unfolding pathway-dependent stability of proteins: vectorial unfolding versus global unfolding. PMID:20095049
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
6YJ0 2020-04-02T00:00:00+0000 0 Solution NMR structure of titin N2A region Ig domain I83
1BPV 1998-08-11T00:00:00+0000 0 TITIN MODULE A71 FROM HUMAN CARDIAC MUSCLE, NMR, 50 STRUCTURES
1G1C 2000-10-11T00:00:00+0000 2.1 I1 DOMAIN FROM TITIN
1NCT 1996-08-13T00:00:00+0000 0 TITIN MODULE M5, N-TERMINALLY EXTENDED, NMR
1NCU 1996-08-13T00:00:00+0000 0 Titin Module M5, N-terminally Extended, NMR
1TIT 1996-02-02T00:00:00+0000 0 TITIN, IG REPEAT 27, NMR, MINIMIZED AVERAGE STRUCTURE
1TIU 1996-02-02T00:00:00+0000 0 TITIN, IG REPEAT 27, NMR, 24 STRUCTURES
1TKI 1998-05-29T00:00:00+0000 2.0 AUTOINHIBITED SERINE KINASE DOMAIN OF THE GIANT MUSCLE PROTEIN TITIN
1TNM 1995-01-17T00:00:00+0000 0 TERTIARY STRUCTURE OF AN IMMUNOGLOBULIN-LIKE DOMAIN FROM THE GIANT MUSCLE PROTEIN TITIN: A NEW MEMBER OF THE I SET
1TNN 1995-01-17T00:00:00+0000 0 Tertiary structure of an immunoglobulin-like domain from the giant muscle protein titin: a new member of the I set

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
90.9 TITIN A2ASS6 TITIN_MOUSE
100.0 Titin Q8WZ42 TITIN_HUMAN